Quantification of CBD, Δ9-THC and Their Isomers in Cannabis-based Drug Matrices by UHPLC-MS: A Comparison Between LTQ and Orbitrap MS Analyzers

Advances in studies of the pharmacological properties of components extracted from the Cannabis plant have led to the exploration of these substances as potential pharmaceutical targets in the treatment of a variety of symptoms and diseases, including pain, inflammation, emesis, multiple sclerosis, neurodegenerative disorders, epilepsy, cancer, cardiovascular disorders, among others. Thus, this work presents a method of quantification of the main therapeutic components of Cannabis by LC-MS applied to drug matrices using two different mass analyzers (LTQ and Orbitrap). The certified cannabinoid standards (cannabinodiol, cannabinol, and cannabifuran, cannabidiol, cannabichromene, cannabicyclol, Δ9-tetrahydrocannabinol, and Δ8-tetrahydrocannabinol, cannabidiolic acid, and Δ9-tetrahydrocannabinolic acid , supplied by Cerilliant (TX, USA) at concentrations of 1 mg mL-1, were dissolved in methanol (neutral cannabinoids) or acetonitrile (acid cannabinoids). Cannabis oil samples (extracted with methanol) were provided by patients/users with legal authorization. Samples were analyzed using a Vanquish UHPLC (Thermo Scientific), Agilent C18 column (2.1×150 mm, 1.9 µm) coupled to the Ion Trap LTQ XL and Orbitrap mass spectrometers (Thermo Scientific) with ESI(±) source and range m/z 50-1000. Fragmentation experiments were performed, and some isomeric standards were distinguished based on fragmentation (MS/MS and MSan) profile and retention time. The method was developed and optimized based on the analysis of the main cannabinoid standards. Sequentially, samples of Cannabis oils used for medicinal purposes were analyzed with the developed method, and their chemical compositions were investigated, with a focus on the detection of cannabinoids. With the acquired MS spectra and evaluation of the chemical composition of the samples, the oils could be qualified according to their main component, i.e., the most abundant cannabinoid.